Application of 5-O-methylvisammioside in preparation of product for treating hyperuricemia

Abstract

The invention belongs to the field of biological medicine, and particularly relates to application of 5-O-methylvisammioside in preparation of a product for treating hyperuricemia. According to the invention, a novel inhibitor 5-O-methylvisammioside of CNT2 is detected, and the novel inhibitor 5-O-methylvisammioside can reduce absorption of intestinal dietary purine nucleoside by inhibiting CNT2 to play a role in reducing uric acid so as to protect uric acid diseases. On the cellular level, the 5-O-methylvisammioside can be competitively combined with the CNT2, and adenosine transport is inhibited. On the animal level, the uric acid concentration of a 5-O-methylvisammioside mouse is more stable, the uric acid concentration can be recovered to the initial uric acid range more quickly, liver and kidney injuries caused by hyperuricemia can be relieved, and meanwhile the intestinal permeability can be improved. The scheme of the invention provides a design thought for designing, synthesizing and developing a novel intestinal purine absorption inhibitor, and provides a new target for clinical treatment of hyperuricemia.

Description

Technical Field

[0002] The invention belongs to the field of biomedicine, and in particular relates to the application of 5-O-methylvisaminol glycoside in the preparation of a product for treating hyperuricemia. Background Art

[0003] Hyperuricemia (HUA) and gout are both chronic metabolic diseases caused by elevated serum uric acid levels due to impaired purine metabolism. However, current clinical medications mainly target the liver and kidneys, and there are no uric acid-lowering drugs that act on the intestinal dietary purine absorption pathway. A large number of epidemiological studies have shown that the common causes of elevated uric acid are excessive consumption of alcohol and purine-rich foods (such as meat and seafood). At the same time, experiments have shown that a low-purine diet can reduce serum uric acid levels in patients with hyperuricemia. Therefore, it can be seen that increased purine intake can increase blood uric acid levels, and inhibiting its gastrointestinal absorption can be used as a link in the prevention and treatment of hyperuricemia.

[0004] Purine is a substance in the human body, which mainly exists in the form of purine nucleotides. The main site of gastrointestinal absorption is the small intestine, and the main form of absorption is nucleosides. The transmembrane transport of nucleosides depends on nucleoside transporters. There are two main types of nucleoside transporters in the human body: equilibrium nucleoside transporters (ENTs or SLC29) and concentration-type nucleoside transporters (CNTs or SLC28). ENTs transport pyrimidine and purine substances by facilitated diffusion and are mainly distributed in the basolateral membrane of intestinal epithelial cells. CNT is a Na+-dependent enriched nucleoside transporter, an active transporter that reversibly transports extracellular nucleosides into cells by concentration gradient. It is mainly distributed in the apical membrane of intestinal epithelial cells, transports purine nucleosides and uridine, and is most highly expressed in the human digestive system.

[0005] In recent years, CNT2 is considered to be the core transporter for intestinal purine nucleoside absorption. It is not only mainly enriched in purine nucleosides in function, but also has a relatively high expression in the intestine, mainly distributed in organs such as the stomach, duodenum, jejunum, and ileum. Existing studies have found that intestinal CNT2 expression is significantly increased in hyperuricemia model animals, but the research on the application of CNT2 inhibitors in hyperuricemia only comes from the KGO-2142 and KGO-2173 compounds discovered in Japan. This compound confirms that inhibiting the CNT2 nucleoside transporter can effectively reduce intestinal dietary purine absorption and lower serum uric acid, but its toxic side effects on important organs such as the liver and kidneys have not yet been verified, which is not conducive to clinical development. Therefore, it is particularly urgent and important to find and develop new uric acid-lowering drug targets or drugs.

[0006] There are three main types of uric acid-lowering drugs currently used in clinical practice: the first type is to inhibit xanthine oxidase to reduce uric acid synthesis, and the representative drugs are allopurinol and febuxostat, both of which are first-line clinical drugs. Allopurinol has related serious skin adverse reactions, and long-term use can cause gastrointestinal discomfort, liver dysfunction, blood system damage and increase the risk of death; febuxostat has significant toxic side effects on the heart and kidneys; the second type is to inhibit the reabsorption of urate by the renal tubules, and the representative drug is benzbromarone. Benzbromarone can cause severe liver damage. The third type is uric acid dissolving drugs, and the representative drug is rasburicase, which is a recombinant urate oxidase. It is expensive and is mainly used for patients with hyperuricemia caused by chemotherapy. The safety of this drug still needs further verification. Clinical drugs mainly target the liver and kidneys, but HUA and gout are chronic metabolic diseases caused by purine metabolism disorders leading to increased serum uric acid. At present, there are no uric acid-lowering drugs that act on the intestinal purine absorption pathway in clinical practice.

[0007] 5-O-methylvisaminol glycoside (hereinafter referred to as AM) is a natural active ingredient from Saposhnikovia divaricata, which has multiple pharmacological activities such as anti-tumor and anti-depression. In recent years, more and more studies have found the pharmacological effects of 5-O-methylvisaminol glycoside, such as analgesia, anti-inflammatory, and energy metabolism. However, no study has found the relationship between 5-O-methylvisaminol glycoside and uric acid diseases. Summary of the invention

[0008] The purpose of the first aspect of the present invention is to provide an application.

[0009] The second aspect of the present invention aims to provide a method.

[0010] In order to achieve the above-mentioned purpose of the present invention, the technical solution adopted by the present invention is:

[0011] The first aspect of the present invention provides the use of 5-O-methylvisaminol glycoside or its derivatives in a1) to a3):

[0012] a1) preparing a CNT2 inhibitor;

[0013] a2) preparing products that inhibit the absorption of purine nucleosides;

[0014] a3) Preparation of products for treating uric acid diseases.

[0015] Preferably, the derivative comprises one of a halogenated product, a nitrated product, a sulfonated product, an esterified product, or an alkoxide.

[0016] Preferably, the alkoxide comprises a salt formed by 5-O-methylvisaminol glycoside and a metal ion.

[0017] Preferably, the uric acid disease refers to a disease associated with abnormal uric acid levels in a living body.

[0018] Preferably, the uric acid disease includes at least one of uric acid nephropathy, hyperuricemia, gout, uric acid arthritis, and kidney stones.

[0019] Preferably, the CNT2 is nucleoside transporter CNT2 (Official Symbol: SLC28A2, NCBI, Gene ID: 9153).

[0020] Preferably, the product includes at least one of medicine and health care product.

[0021] Preferably, the product comprises pharmaceutically acceptable excipients.

[0022] Preferably, the pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrities, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, and carriers.

[0023] Furthermore, in order to facilitate medication, the active ingredient 5-O-methylvisaminol glycoside can be processed into a specific dosage form with any one or more pharmaceutically acceptable excipients. These excipients can be diluents (such as starch, pregelatinized starch, dextrin, sucrose, lactose, mannitol and microcrystalline cellulose, etc.), absorbents (such as calcium sulfate, calcium hydrogen phosphate, light magnesium oxide and calcium carbonate, etc.), wetting agents (such as water and ethanol, etc.), binders (such as hydroxypropyl methylcellulose, povidone, starch slurry and syrup, etc.), disintegrants (such as dry starch, sodium hydroxymethyl starch, low-substituted hydroxypropyl cellulose, effervescent disintegrants and cross-linked polyvinylpyrrolidone, etc.), lubricants (magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol and micropowder silica gel, etc.), colorants (such as titanium dioxide, sunset yellow, methylene blue and medicinal iron oxide, etc.), coating materials (such as acrylic resin, hydroxypropyl methylcellulose and povidone, etc.), solvents (such as water for injection, ethanol, propylene glycol and glycerol, etc.), acid-base regulators (such as hydrochloric acid, lactic acid, sodium hydroxide, tartaric acid and sodium tartrate, etc.), antioxidants (such as sodium sulfite, sodium pyrosulfite and sodium thiosulfate, etc.), antibacterial agents (such as phenol, benzyl alcohol and thimerosal, etc.), and isotonic regulators (such as sodium chloride and glucose, etc.).

[0024] Preferably, the dosage form of the product includes a dosage form for enteral administration or a dosage form for parenteral administration.

[0025] Preferably, the dosage form for administration via the gastrointestinal tract includes at least one of powders, tablets, granules, capsules, sustained-release agents, solutions, dry suspensions, effervescent tablets, emulsions, suspensions, syrups, drops, and chewable tablets.

[0026] Furthermore, the dosage forms for administration through the gastrointestinal tract include but are not limited to enteric-coated tablets, coated tablets, film-coated tablets, sugar-coated tablets, dispersible tablets, sucking tablets, chewable tablets, effervescent tablets, scratched tablets, sustained-release and controlled-release dosage forms such as sustained-release tablets, sustained-release coated tablets, controlled-release tablets, orally disintegrating tablets, lozenges, oral patches, etc.

[0027] Preferably, the non-intestinal administration dosage form includes at least one of an injection dosage form, a respiratory tract administration dosage form, a skin administration dosage form, a mucosal administration dosage form, and a cavity administration dosage form.

[0028] Furthermore, the injectable dosage forms include but are not limited to injection solutions, injection solutions, intravenous injection solutions, injection suspensions, sterile powders for injection, intravenous injections, water injections, injection emulsions, powder injections, injections, sterile powder injections, freeze-dried powder injections, etc.

[0029] The second aspect of the present invention provides a method for inhibiting CNT2 activity in vitro for non-therapeutic purposes, comprising the step of treating cells with 5-O-methylvisaminol glycoside.

[0030] The beneficial effects of the present invention are:

[0031] The present invention detects a new inhibitor of CNT2, 5-O-methylvisaminol glycoside, which can reduce the absorption of dietary purine nucleosides in the intestine by inhibiting CNT2 to exert a uric acid-lowering effect, thereby protecting against uric acid diseases. At the cellular level, 5-O-methylvisaminol glycoside can competitively bind to CNT2 and inhibit adenosine transport. At the animal level, the uric acid concentration of mice treated with 5-O-methylvisaminol glycoside is more stable and recovers to the initial uric acid range more quickly, which can alleviate liver and kidney damage caused by hyperuricemia and improve intestinal permeability. The scheme of the present invention provides a design idea for the design, synthesis and development of a new intestinal purine absorption inhibitor, and provides a new target for the clinical treatment of hyperuricemia. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Molecular docking of adenosine (A), 5-O-methylvisaminol (B), and positive control inhibitor (C) and 3 H adenosine uptake experiment (D) and docking score results of each group (E).

[0033] Figure 2The results of 5-O-methylvisaminol glycoside on CNT1 (A), CNT3 (B) and docking score (C).

[0034] Figure 3 This is a graph showing the effect of a single dose of 5-O-methylvisaminol glycoside on serum uric acid in mice fed a high-purine diet.

[0035] Figure 4 The uric acid-lowering effect of 5-O-methylvisaminol glycoside on mice with chronic hyperuricemia.

[0036] Figure 5 Figure 5 shows the protective effect of 5-O-methylvisaminol glycoside on important organs of mice with chronic hyperuricemia; AB shows HE pathological staining of liver and kidney; and C shows the results of intestinal permeability experiment.

[0037] Reference symbols: **** indicates P<0.001 compared with the NC group; # indicates P<0.05 compared with the OE-CNT2 group; #### indicates P<0.0001 compared with the HUA group. DETAILED DESCRIPTION

[0038] The following will be combined with the embodiments to clearly and completely describe the concept of the present invention and the technical effects produced, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0039] The reagent materials used in the embodiments of the present invention are all commercially available or can be prepared. The reagents used in the following embodiments are as follows: yeast extract, CAS NO.: 8013-01-2; potassium oxonate, CAS NO.: 2207-75-2; 5-O-methylvisaminol glycoside, CAS NO.: 84272-85-5; CNT2 inhibitor, CAS NO.: 880155-70-4; adenosine, CAS NO.: 58-61-7.

[0040] Example 1 Compound Molecular Docking Using CNT2 Protein as Receptor

[0041] 1) Virtual screening and flexible docking

[0042] The CNT2 protein (Official Symbol: SLC28A2, NCBI, Gene ID: 9153) was used as the target to screen for potential binding compounds. Two databases were selected: one was the internal natural product database (PMID: 38669781, 34775203), which contains 205 herbs and 811 natural products; the other was the saccharide and glycoside compound library, which was purchased from the Kashma Mall (Saccharide and Glycoside Natural Product Library, 345natural products). Using the CNT2 protein as the docking conformation, potential CNT2 inhibitors were identified through 3D shape similarity screening, and the top 8 compounds with the highest similarity values ​​were selected for further study. 5-O-methylvisaminol glycoside, one of the 8 compounds, is a natural compound extracted from Saposhnikovia divaricata, which has obvious antipyretic, analgesic and anti-inflammatory effects. The results are as follows Figure 1 As shown in A~C,E.

[0043] By docking with CNT2 protein, 5-O-methylvisaminol glycoside and CNT2 can bind to each other, and its docking score is greater than adenosine and known CNT2 inhibitors ( Figure 1 In addition, docking analysis showed that there was partial overlap between the conformations of 5-O-methylvisaminol and adenosine, indicating their structural similarity, suggesting that it may inhibit adenosine transport by competing for adenosine binding sites to play a role in lowering uric acid ( Figure 1 C). At the same time, the selectivity of 5-O-methylvisaminol glycoside to other proteins in the CNTs family, CNT1 and CNT3, was analyzed, and it was found that 5-O-methylvisaminol glycoside had the highest selectivity for CNT2 (the results are shown in Figure 2 shown).

[0044] Example 2 In vitro inhibitory effect of 5-O-methylvisaminol on CNT2

[0045] 1) Poly-D-lysine (PDL) coated 96-well plate

[0046] A 96-well plate was coated with 0.1 mg / mL poly-D-lysine for 24 h, and then the poly-D-lysine was discarded and dried in an oven at 37° C. for 12 h before use.

[0047] 2) Cell transfection

[0048] When the human embryonic kidney cells (HEK293T cells) grow and fuse to 90%, the HEK293T cells are inoculated into a 96-well plate coated with PDL, placed in a 37°C, 5% CO2 incubator for 18h to 24h, and when the cell fusion rate is about 70% to 80%, CNT2 plasmid transient transfection is performed. The CNT2 plasmid is designed from Qingke Biotechnology Company, pcDNA3.1 (+) is selected as the expression vector, the active fragment of the target gene sequence is the full length of CNT2 (Gene ID: 9153), and the gene is marked with 3xFlag.

[0049] The specific transfection steps are as follows: add 25 μL of reduced serum medium (Opti-MEM, glibco, 31985070) to two 1.5 mL EP tubes (tube 1 and tube 2), then add 500 ng of the plasmid in 1) and 1 μL of P3000 to tube 1. TM (Thermo fisher, L3000015) and mix well; add 0.75 μL of Lipo 3000 to tube 2. TM , vortex the sample tube for 10 seconds and let it stand for 5 minutes; then mix the liquid in the two tubes, vortex for 10 seconds, let it stand for 25 minutes, and evenly drop it into the wells with 500 μL / well new culture medium, the addition amount is 10 μL / well, and place it in a 37°C, 5% CO2 incubator for 24 hours.

[0050] 3) 3 H adenosine uptake assay

[0051] (1) Preparation of Na + Uptake buffer: The formula is: 140mM NaCl, 2mM KCl, 1mM MgCl2, 2mM CaCl2, 10mM HEPES, 5mM Tris, 5mM D-glucose. After preparation, use 0.1M NaOH to adjust the pH to about 7.4, then filter with a 0.22μm microporous filter membrane and store at 4°C for future use.

[0052] (2) Preparation of drug uptake buffer: Dissolve 5-O-methylvisaminol glycoside powder in DMSO to obtain a 50 mM stock solution; + Dilute with uptake buffer to obtain the desired concentration of 10 μM. It is best to prepare it before use.

[0053] (3) Preparation of 3 Intake solution of H-adenosine and 5-O-methylvisaside: with Na + Uptake buffer was prepared at a concentration of 100 μM 3The H-adenosine solution was then mixed with an equal volume of 5-O-methylvisaminol glycoside solution dissolved in (2) uptake buffer to obtain a final concentration of 50 μM. 3 Uptake mixture of H-adenosine and 10 μM 5-O-methylvisaminidine.

[0054] (4) 3 Specific steps of H adenosine uptake experiment: discard the culture medium in HEK293T cells transfected with CNT2, wash the cells 3 times with uptake buffer, 200 μL each time. Add 245 μL of 5-O-methylvisaminol glycoside (10 μM) uptake buffer for pre-incubation for 15 minutes, add uptake buffer containing both drugs and adenosine after pre-incubation, immediately discard the liquid in the well after 15 minutes of incubation, add ice-cold DPBS buffer to wash the cells 3 times, 200 μL each time. Finally, add 150 μL of 0.1M NaOH to lyse the cells for 10 minutes, add 800 μL of liquid scintillation fluid (Revvity, 6013329), and transfer to a liquid scintillator to record the change of radioactivity.

[0055] Figure 1 D in the figure is 5-O-methylvisaminol glycoside and CNT2 overexpression (OE-CNT2) 3 The uptake of H-adenosine suggests that 5-O-methylvisaminol glycoside can competitively bind to CNT2 and inhibit adenosine transport.

[0056] Example 3 Effect of a single dose of 5-O-methylvisaminol on serum uric acid in mice fed a high-purine diet

[0057] 1) Experimental animal grouping

[0058] Six-week-old SPF male C57 mice weighing 22±2g were selected and divided into three groups according to the average weight, and grouped according to Table 1 below. The temperature of all animals was controlled at 24℃~26℃, and the relative humidity was controlled at 40%~60%, with 8 mice per cage. The experiment was carried out after 1 week of adaptive feeding. The relevant animal experiments were approved by the Ethics Review Committee and relevant permits were obtained.

[0059] 2) Effect of single dose administration on uric acid

[0060] Each group of mice was required to perform orbital blood sampling before administration to detect the uric acid value of each mouse before administration. Each group of mice was intraperitoneally injected with 300 mg / kg of potassium oxonate solution and intragastrically administered with 15 mg / kg of yeast extract solution (solvent is 0.5wt% CMC-Na), wherein the administration group was mixed with low-dose (5-O-methylvisaminol glycoside final concentration of 10 mg / kg) and high-dose (5-O-methylvisaminol glycoside final concentration of 20 mg / kg) 5-O-methylvisaminol glycoside and yeast extract solution and administered simultaneously.

[0061] After administration, blood samples were collected from each group of mice through orbital bleeding every 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, and 8 h. After standing at room temperature for 30 min, the mice were centrifuged at 4 °C and 3000 rpm for 15 min. The upper serum was taken and the uric acid level in the serum was determined using a uric acid test kit (Nanjing Jiancheng Bioengineering Institute, C012-2-1).

[0062] Table 1 Grouping and oral administration of mice in the single-dose 5-O-methylvisaminol glycoside in vivo uric acid-lowering activity test

[0063]

[0064]

[0065] The drug preparation and concentration of each group were: 0.5wt% sodium carboxymethylcellulose as drug solvent, potassium oxonate (36mg / mL), yeast extract (1.8g / mL), 5-O-methylvisaminol low-dose group (1.2mg / mL) and 5-O-methylvisaminol high-dose group (2.4mg / mL). The injection was administered in a volume of 100μL / 12g.

[0066] Figure 3 This is a graph showing the effect of a single dose of 5-O-methylvisaminol on serum uric acid in mice fed a high-purine diet, indicating that the uric acid concentration in mice treated with 5-O-methylvisaminol was more stable and recovered to the initial uric acid range more quickly.

[0067] Example 4 Protective effect of 5-O-methylvisamidoside on important organs in a mouse model of chronic hyperuricemia

[0068] 1) Experimental animal grouping

[0069] Six-week-old SPF male C57 mice weighing 22±2g were selected and divided into 4 groups according to the average weight, and grouped according to Table 2 below. The temperature of all animals was controlled at 24℃~26℃, and the relative humidity was controlled at 40%~60%, with 8 mice per cage. The experiment was carried out after 1 week of adaptive feeding. The relevant animal experiments were approved by the Ethics Review Committee and relevant permits were obtained.

[0070] 2) Establishment of chronic hyperuricemia model

[0071] During the experiment, mice ate and drank water normally. Except for the blank group, mice in each group were intraperitoneally injected with 300 mg / kg potassium oxonate solution and gavaged with 15 mg / kg yeast extract solution (solvent was 0.5 wt% CMC-Na) at 9:30 every day. The low-dose (final concentration of 5-O-methylvisaminol glycoside was 10 mg / kg) and high-dose (final concentration of 5-O-methylvisaminol glycoside was 20 mg / kg) 5-O-methylvisaminol glycoside were mixed with yeast extract solution and administered at the same time. The blank control group was gavaged and injected with the same volume of 0.5 wt% sodium carboxymethyl cellulose. The experiment lasted for a total of 21 days. After the end of the administration on the 21st day, blood was collected and the mice were killed. At the time of death, samples of kidney, liver and intestinal tissue (duodenum, jejunum, ileum) were retained, part of which was immersed in paraformaldehyde fixative, and part was stored at -80°C.

[0072] Table 2 Grouping and oral administration of mice in the experiment of 5-O-methylvisaminol glycoside protecting important organs in mice with chronic hyperuricemia

[0073]

[0074]

[0075] The drug preparation and concentration of each group were: 0.5wt% sodium carboxymethylcellulose as drug solvent, potassium oxonate (36mg / mL), yeast extract (1.8g / mL), 5-O-methylvisaminol low-dose group (1.2mg / mL) and 5-O-methylvisaminol high-dose group (2.4mg / mL). The injection was administered in a volume of 100μL / 12g.

[0076] 3) Intestinal permeability FITC experiment

[0077] The treatment of mice was the same as described in 2) above to establish a chronic hyperuricemia model mouse. On the 21st day after modeling, the in vivo permeability assay was performed using the FITC-labeled dextran (4kD, Sigma, 46944) method to evaluate the barrier function. After fasting for 4 hours, the mice were gavaged with 400 mg / kg FITC-labeled dextran. After 4 hours, the mice were anesthetized, blood was collected by enucleation of the eyeballs, and serum was obtained by centrifugation at 4°C, 3000 rpm, and 15 minutes after standing for 30 minutes. The intestinal permeability of each group of mice was obtained by measuring the fluorescence intensity of each sample (excitation wavelength 490nm; emission wavelength 520nm; FITC-dextran concentration was determined by the standard curve generated by the serial dilution of FITC-dextran).

[0078] 4) Sample processing and determination

[0079] Blood: About 500 μL of blood was allowed to stand at room temperature for 30 min, then centrifuged at 3000 rpm for 15 min at 4° C. Serum was collected and stored at −20° C. Uric acid (UA) in serum was measured using a uric acid test kit (Uric acid test kit C012-2-1, Nanjing Jiancheng Bioengineering Institute).

[0080] Kidney: After killing the mice, the kidney tissue was quickly separated and the renal membrane was peeled off. Both kidneys were placed on a white background and photographed. The right kidney was taken and placed in paraformaldehyde fixative for HE staining.

[0081] Liver: After killing the mice, the liver tissue was quickly separated and photographed intact against a white background. The left lobe of the mice was uniformly removed and placed in paraformaldehyde fixative for HE staining.

[0082] Intestine: After killing the mice, the duodenum, jejunum, and ileum were removed respectively. One part was stored in paraformaldehyde fixative for HE staining, and the other part was stored at -80℃.

[0083] Figure 4 The uric acid-lowering effect of 5-O-methylvisaminol glycoside on chronic hyperuricemia mice. The mouse model of chronic hyperuricemia was established by oral administration of high-purine diet yeast extract combined with intraperitoneal injection of uricase inhibitor potassium oxonate for 4 weeks. The blood collection results after 4 weeks showed that the serum uric acid of 5-O-methylvisaminol glycoside was significantly lower than that of the HUA model group, indicating that it can achieve the effect of lowering uric acid.

[0084] Figure 5 The protective effect of 5-O-methylvisaminol glycoside on the important organs of mice with chronic hyperuricemia: AB are HE pathological staining images of the liver and kidney, and C is the result of the intestinal permeability experiment. In the chronic hyperuricemia mouse model, it can be found that when 5-O-methylvisaminol glycoside is used, the liver and kidney damage caused by hyperuricemia can be alleviated, and the intestinal permeability can be improved. This shows that 5-O-methylvisaminol glycoside can not only play a role in lowering uric acid, but also improve the pathological changes of organs caused by hyperuricemia.

Claims

1. Application of 5-O-methylvisaminol glycoside or its derivatives in a1) to a3): a1) preparing a CNT2 inhibitor; a2) preparing products that inhibit the absorption of purine nucleosides; a3) Preparation of products for treating uric acid diseases.

2. The use according to claim 1, characterized in that: The derivative includes one of a halogenated product, a nitrated product, a sulfonated product, an esterified product, or an alkoxide.

3. The use according to claim 2, characterized in that: The alkoxide includes a salt formed by 5-O-methylvisaminol glycoside and a metal ion.

4. The use according to claim 1, characterized in that: The uric acid disease includes at least one of uric acid nephropathy, hyperuricemia, gout, uric acid arthritis, and kidney stones.

5. The use according to claim 1, characterized in that: The product includes at least one of medicine and health care product.

6. The use according to claim 5, characterized in that: The product includes pharmaceutically acceptable excipients.

7. The use according to claim 6, characterized in that: The pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrities, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, and carriers.

8. The use according to claim 5, characterized in that: The dosage form of the product includes a dosage form for gastrointestinal administration or a dosage form for parenteral administration; Preferably, the dosage form for administration via the gastrointestinal tract includes at least one of powder, tablet, granule, capsule, sustained-release agent, solution, dry suspension, effervescent tablet, emulsion, suspension, syrup, drops, and chewable tablet; Preferably, the non-intestinal administration dosage form includes at least one of an injection dosage form, a respiratory tract administration dosage form, a skin administration dosage form, a mucosal administration dosage form, and a cavity administration dosage form.

9. The use according to claim 5, characterized in that: The product is administered to a mammal; Preferably, the mammal includes at least one of mice, cats, dogs, rabbits, pigs, cows, sheep and humans.

10. A method for inhibiting CNT2 activity in vitro for non-therapeutic purposes, comprising the step of treating cells with 5-O-methylvisaminoid glycoside.

Images